** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** ANAPLASMA MARGINALEIS AN INTRAERYTHROCYTIC RICKETTSIAL PATHOGEN AND CAUSES THE MOST PREVALENT TICK-BORNE INFECTION OF CATTLE BOTH WORLDWIDE AND WITHIN THE U.S. IN THE U.S., THE MAJOR IMPACT IS EPISODIC OUTBREAKS IN WHICH MORBIDITY IS DUE TO SEVERE ANEMIA AND THE MEAN CASE FATALITY RATE HAS BEEN REPORTED AT 36%. ECONOMIC LOSSES DUE TO ANAPLASMOSIS ARE ESTIMATED AT ~$300 MILLION/YEAR. THERE ARE NO VACCINES CURRENTLY LICENSED IN THE U.S. THOSE USED ELSEWHERE CARRY THE RISK OF TRANSMITTING EMERGING PATHOGENS AND RELY ON THE COLD CHAIN. OUTER MEMBRANE PROTEIN (OMP) PREPARATIONS AND OMP COMPLEXES HAVE BEEN SHOWN TO INDUCE ROBUST PROTECTION. HOWEVER, THESE VACCINATION REGIMES REQUIRE TECHNICAL EXPERTISE, A COLD CHAIN, AND ARE NOT PRACTICAL FOR LARGE SCALE PRODUCTION. WE PROPOSE TO DEVELOP A VACCINE AGAINST ANAPLASMOSIS BASED ON THE OMP PREPARATIONS/COMPLEXES. WE WILL TEST THE HYPOTHESIS THAT THE PROTECTIVE CAPACITY OF OMP PREPARATIONS/COMPLEXES CAN BE RECAPITULATED WITH A DEFINED SET OF VACCINE CANDIDATES KNOWN TO BE PRESENT IN THE OMP PREPARATIONS. WE WILL DELIVER A COCKTAIL OF VACCINE CANDIDATES AS A GENETIC (OR DNA) VACCINE USING A GENE GUN. THIS PLATFORM CAN DELIVER AS MANY CANDIDATES AS NEEDED AND DOES NOT RELY ON A COLD CHAIN. WE WILL EMPLOY TICK CHALLENGES TO ENSURE RIGOROUS TESTING OF OUR VACCINE. THE PROJECT WILL INCORPORATE HOMOLOGOUS, HETEROLOGOUS AND FIELD CHALLENGE SCENARIOS. WE WILL TEST WHETHER WE CAN REDUCE THE NUMBER OF IMMUNOGENS IN THE VACCINE WITHOUT LOSING EFFICACY, AND WHETHER A VACCINE BASED ON US VARIANTS WILL PROVIDE PROTECTION IN A GLOBAL CONTEXT.